rs369869865
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001378120.1(MBD5):c.961A>G(p.Met321Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M321T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378120.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.961A>G | p.Met321Val | missense_variant | 8/14 | ENST00000642680.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.961A>G | p.Met321Val | missense_variant | 8/14 | NM_001378120.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250892Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135592
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461666Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727124
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74292
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 1 Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | MBD5 NM_018328.4 exon 9 p.Met321Val (c.961A>G):This variant has not been reported in the literature but is present in 4/126318 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs369869865). This variant is present in ClinVar (Variation ID:206065). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 11, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2018 | The p.M321V variant (also known as c.961A>G), located in coding exon 4 of the MBD5 gene, results from an A to G substitution at nucleotide position 961. The methionine at codon 321 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at